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Goldstein, Y.

Publications and source records attributed to Goldstein, Y..

4 recordsLinked to original sources

Remote and Independent Detection of Human Stress Using Sweat and AI

Previous studies exploring human sweat ducts as biological antennas in the sub-THz range have shown that the electromagnetic (EM) response of the skin is modulated by the persons mental and physical stress. These findings naturally raised hopes of a new remote avenue for detecting human stress. However, as those studies unmasked stress using correlations with well-established markers such as the Galvanic Skin Response (GSR), the question of whether the EM response could serve as an independent marker of stress remained unanswered. Here, we provide a positive answer to this question by showing that machine learning models trained on EM reflections from 21 participants, subjected to physical and mental stress, were able to estimate the presence of stress in a signal from a new participant, in a matter of seconds, with above 90% accuracy.

biophysics↗

Cyclin-dependent kinase 9 inhibitors as oncogene signaling modulators in combination with targeted therapy for the treatment of colorectal cancer

BackgroundColorectal cancer (CRC) is the second deadliest cancer worldwide and new treatment options are urgently needed. Cyclin dependent kinase 9 (CDK9) promotes aberrant RNA transcription in cancer and is a promising target for cancer therapies. MethodsUsing CRC cell lines as well as newly established patient-derived organoid models of CRC, we studied the clinically promising CDK9 inhibitors (AZD4573, BAY1125152/VIP152/enitociclib, and NVP2) to determine their therapeutic potential. We investigated the efficacy and mechanisms of action through cell growth and cytotoxicity assays, RNAseq, immunoblotting, and IHC. ResultsWe found CDK9 inhibitors to be highly potent against CRC, through suppression of proliferation and induction of apoptosis. Our results demonstrated CDK9 inhibitors to be broadly active against a set of CRC models derived from a diverse patient population. Our mechanistic studies showed significant suppression of the Mitogen-active protein kinase (MAPK) signaling pathway due to CDK9 inhibitor treatment, suggesting that CDK9 inhibitor efficacy could be enhanced when combined with MAPK pathway inhibitors. As proof-of-concept, we found that CDK9 inhibitors and MEK inhibitors could be combined to synergistically suppress CRC growth and survival. ConclusionsCDK9 inhibitors show promising activity against patient-derived models of CRC. MAPK signaling is particularly suppressed by CDK9 inhibitors. Combining CDK9 inhibitors and targeted therapy against MAPK signaling pathway may be a viable strategy worthy of further investigation preclinically and clinically. State of translational relevanceNovel therapies for chemotherapy-refractory CRC remain urgently needed. Rapid validation of efficacy in appropriate translational models can provide the necessary rationale to test new therapies in clinical trials. Using newly established patient-derived organoids, we validate the preclinical efficacy of transcriptional CDK9 inhibitors against CRC. This is a therapeutic class that has been scarcely evaluated for efficacy against CRC. We found that CDK9 inhibitors potently inhibit patient-derived organoid models of CRC. Our mechanistic work also reveals that clinically achievable concentrations of CDK9 inhibitor treatment results in suppression of MAPK signaling. As proof-of-concept of the potential actionability of our findings, we demonstrate that CDK9 inhibitors can be combined with MEK inhibitors to synergistically suppress CRC growth. Our study provides new patient-derived CRC models as a resource available to others for therapeutic testing, as well as a roadmap for novel hypotheses about synergistic combination treatments using CDK9 inhibitors.

cancer biology↗

Title: Diurnal rhythms in durum wheat triggered by Rhopalosiphum padi (bird cherry-oat 2 aphid)

Wheat is a staple crop and one of the most widely consumed grains globally. Wheat yields can experience significant losses due to the damaging effects of herbivore infestation. However, little is known about the effect aphids have on the natural diurnal rhythms in plants. Our time-series transcriptomics and metabolomics study reveal intriguing molecular changes occurring in plant diurnal rhythmicity upon aphid infestation. Under control conditions, 15,366 out of the 66,559 genes in the tetraploid wheat cultivar Svevo, representing approximately 25% of the transcriptome, exhibited diurnal rhythmicity. Upon aphid infestation, 5,682 genes lost their rhythmicity, while additional 5,203 genes began to exhibit diurnal rhythmicity. The aphid-induced rhythmic genes were enriched in GO terms associated with plant defense, such as protein phosphorylation and cellular response to ABA and were enriched with motifs of the WRKY transcription factor families. Conversely, the genes that lost rhythmicity due to aphid infestation were enriched with motifs of the TCP and ERF transcription factor families. While the core circadian clock genes maintain their rhythmicity during infestation, we observed that approximately 60% of rhythmic genes experience disruptions in their rhythms during aphid infestation. These changes can influence both the plants growth and development processes as well as defense responses. Furthermore, analysis of rhythmic metabolite composition revealed that several monoterpenoids gained rhythmic activity under infestation, while saccharides retained their rhythmic patterns. Our findings highlight the ability of insect infestation to disrupt the natural diurnal cycles in plants, expanding our knowledge of the complex interactions between plants and insects.

plant biology↗

Diurnal rhythmicity in salivary effector expression and metabolism shapes aphid performance on wheat plants

Diurnal rhythms influence insect behavior, physiology, and metabolism, optimizing their performance by adapting to daily changes in the environment. While their impact on agricultural pests has been briefly explored, our understanding of how these rhythms drive adaptative responses in pest biology and influence host colonization remains elusive. Here, we show that a notorious global aphid pest, Rhopalosiphum padi, exhibits distinct diurnal patterns in feeding behavior, with elevated honeydew excretion at night and extended phloem salivation during early nighttime. Temporal aphid transcriptome profiling reveals four diurnally rhythmic clusters, two of which peak at night, exhibiting enrichment in carbohydrate and amino acid metabolism. Beyond the established role in manipulating host responses and allowing sustained feeding, our study reveals novel evidence of cyclical fluctuations in salivary effector expression in an insect species. Silencing key effector genes, peaking in expression during the increased nighttime salivation, results in a more pronounced reduction in aphid excretion activity on host plants during the night compared to the day, a phenomenon not observed on artificial diets. A better understanding of aphid diurnal rhythms and their roles in shaping aphid performance provides a promising avenue to refine and optimize pest management, granting a strategic advantage for minimizing crop damage.

systems biology↗